The broad objectives of the proposed research are to understand the mechanisms of genetic control of the immune response; to determine how the thymus exerts its suppressive effect during neonatal tolerance induction; to ascertain what are the surface characteristics of lymphocytes responsible for their homing to the gut-associated lymphoid tissue (GALT); and to establish whether lymphocytes bearing surface IgD-like molecules have different properties from lymphocytes bearing other surface immunoglobulins. Gene action in the control of the immune response will be studied in two systems. In one, protein antigens, response to which we have previously shown to be controlled by genes linked to the H-2 locus in mice, will be used. In the other, two polypeptide antibiotics, with which we have recently been working, will be used. These antibiotics, namely bacitracin A and gramicidin, can be conjugated with haptens at a few, well defined sites, and different strains of mice show marked differences in the antibodies they produce to the conjugates. We plan to determine whether the antibody responses are oligoclonal, and whether the antibody differences are controlled by genes linked to the immunoglobulin genes or the H-2 locus or by any of the other known Ir genes. Thymic and thymus-derived (T) cell suppression during the induction of immunological tolerance will be examined in the rat model of neonatal tolerance with which we have been working for the past few years. Experiments on homing to GALT and the factors affecting differentiation ot IgA producing plasma cells will be continued in the Balb/c mouse system we have established and the properties of IgD bearing lymphocytes will be examined in this system and in in vitro culture.